Detailed clinicopathological characteristics and possible lymphomagenesis of type II intestinal enteropathy-associated T-cell lymphoma

• Project/Area Number: 25460444
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Fukuoka University
• Principal Investigator: Takeshita Morishige 福岡大学, 医学部, 教授 (90171636)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Shotaro 岩手医科大学, 医学部, 准教授 (10243932) ; 石塚 賢治 鹿児島大学, 医学部, 教授 (10441742)
• Co-Investigator(Renkei-kenkyūsha): ISHITSUKA Kenji 鹿児島大学, 医学部, 教授 (10441742)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: enteropathy / T-cell lymphoma / C-MET / C-MYC / FISH / IEL / BCL2 / 消化管 / 腸管症 / Ｔ細胞リンパ腫 / c-Met / c-Myc / Bcl2

Outline of Final Research Achievements

Twenty-six Japanese cases of type II enteropathy-associated T-cell lymphoma (EATL) were examined. Intramucosal tumor cell spread and a zone of neoplastic intraepithelial lymphocytes (IELs) neighboring the main tumors were detected in 20 (91%) and 17 (77%) of 22 cases, respectively. Outside of the IEL zone, enteropathy with reactive small IELs and villous atrophy was detected in 11 cases (50%). Lymphoma cells expressed C-MET, p-MEK1/2, C-MYC and BCL-2 in 18 (78%), 21 (91%), 11 (42%) and 19 (73%) cases, respectively. FISH revealed chromosomal loci 7q31 (C-MET) and 8q24 (C-MYC) were amplified in 11 (65%) and 12 (71%) of 17 cases, respectively. Gain of 7q31 and C-MET expression were significantly higher in type II cases than those with peripheral CD8-positive T-cell or CD56-positive NK-cell lymphoma (P<0.01). Enteropathy partly presents near the IEL zone, and C-MET-MAPK pathway and C-MYC-BCL2-mediated cell survival may play important roles in lymphomagenesis in type II EATL.

Research Products

• [Journal Article] High expression of intestinal homing receptor CD103 in adult T-cell leukemia/lymphoma, similar to 2 other CD8+ T-cell lymphomas. (2016)
  • Author(s): Ishibashi H, Nimura S, Ishitsuka K, Mihashi Y, Mizoguchi M, Nakamura S, Okamura S, Momosaki S, Aoyagi K, Sakisaka S, Takeshita M.
  • Journal Title: Am J Surg Pathol Volume: 40 Issue: 4 Pages: 462-470
  • DOI: 10.1097/pas.0000000000000597
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] UGT1A1 *6 polymorphism predicts outcome in elderly patients with relapsed or refractory diffuse large B-cell lymphoma treated with carboplatin, dexamethasone, etoposide and irinotecan. (2015)
  • Author(s): Yamasaki S, Tanimoto K, Kohno K, Kadowaki M, Takase K, Kondo S, Kubota A,Takeshita M, Okamura S.
  • Journal Title: Ann Hematol Volume: 94 Issue: 1 Pages: 65-69
  • DOI: 10.1007/s00277-014-2170-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enhanced antitumor effects of novel intracellular delivery of an active form of (2015)
  • Author(s): Setoguchi S, Watase D, Matsunaga K, Matsubara M, Kubo Y, Kusuda M, Nagata-Akaho N, Enjoji M, Nakashima M, Takeshita M, et al
  • Journal Title: Cancer Prev Res Volume: 8 Pages: 129-138
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinicopathological characteristics and rituximab-plus cytotoxic therapies in patients with rheumatoid arthritis and methotrexate- associated large B-lymphoproliferative disorders. (2015)
  • Author(s): Yamada K, Oshiro Y, Okamura S, Fujisaki T, Kondo S, Nakayama Y, Suematsu E, Tamura K, Takeshita M.
  • Journal Title: Histopathol Volume: 67 Issue: 1 Pages: 70-80
  • DOI: 10.1111/his.12627
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] WRN protein as a novel erythroblast immunohistochemical marker with applications for the diagnosis of Werner syndrome (2014)
  • Author(s): Sadahira Y, Sugihara T, Fujiwara H, Nishimura H, Suetsugu Y, Takeshita M, Okamura S, Goto M.
  • Journal Title: Virchows Arch Volume: 466 Issue: 3 Pages: 343-350
  • DOI: 10.1007/s00428-014-1703-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Detailed clinicopathological characteristics and possible lymphomagenesis of type Ⅱ intestinal enteropathy-associated T-cell lymphoma in Japan. (2014)
  • Author(s): Kanta Kikuma, Kozue Yamada, Shotaro Nakamura,Akiko Ogami, Satoshi Nimura, Minako Hirahashi, Hirotoshi Yonemasu, Shogo Urabe, Shinji Naito, Yasumasa Matsuki,Yoshito Sadahira, Morishige Takeshita
  • Journal Title: Human Pathology Volume: 45 Issue: 6 Pages: 1276-1284
  • DOI: 10.1016/j.humpath.2013.10.038
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] T/NK細胞リンパ腫の細胞性格に関する考察 －腫瘍細胞の性格を知り治療につなげる医療. (2014)
  • Author(s): 竹下盛重、山田梢、中山吉福
  • Journal Title: 日臨細胞九州会誌 Volume: 5 Pages: 5-11
  • Peer Reviewed / Open Access
• [Journal Article] 成人T細胞白血病/リンパ腫を含む消化管T/NK細胞リンパ腫の臨床病理学的特徴. (2014)
  • Author(s): 竹下盛重、二村聡、菊間幹太、山田梢、石橋英樹、他6名
  • Journal Title: 胃と腸 Volume: 49 Pages: 769-781
• [Journal Article] 成人T細胞白血病/リンパ腫を含む消化管T/NK細胞リンパ腫の臨床病理学的特徴 (2014)
  • Author(s): 竹下盛重、二村聡、菊間幹太、山田梢、石橋英樹、中村昌太郎
  • Journal Title: 胃と腸 Volume: 49(5)
• [Presentation] I型腸症関連T細胞リンパ腫4例における主病巣および周囲粘膜の病理像。 (2016)
  • Author(s): 二村聡、石橋英樹、神尾多喜治、竹下盛重。
  • Organizer: 105回日本病理学会総会
  • Place of Presentation: 仙台市
  • Year and Date: 2016-05-12
• [Presentation] 消化管悪性リンパ腫の診断-B, T/NK細胞リンパ腫の解説 （主にT細胞リンパ腫を中心に） (2016)
  • Author(s): 竹下盛重
  • Organizer: 第29回JCRミッドウンターセミナー(日本放射線学会専門医会)
  • Place of Presentation: 福岡市
  • Year and Date: 2016-01-23
  • Invited
• [Presentation] 胃・腸管T細胞リンパ腫の病理診断． (2015)
  • Author(s): 二村聡、石橋英樹、竹下盛重。
  • Organizer: 104回日本病理学会総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-04-30
• [Presentation] 消化管成人T細胞白血病/リンパ腫の病理的所見とaEB7integrin CD103の反応 (2014)
  • Author(s): 山田梢、二村聡、石橋英樹、中山吉福、竹下盛重
  • Organizer: 日本病理学会総会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 消化管成人T細胞性白血病/リンパ腫（ATL/L)の病理的特徴とαEβ7integrinCD103の反応 (2014)
  • Author(s): 山田梢、二村聡、石橋英樹、中山吉福、竹下盛重
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会議場
• [Book] わかりやすい病理学 (2016)
  • Author(s): 竹下盛重(分担出筆）
  • Total Pages: 347
  • Publisher: 南江堂
• [Book] 細胞診ガイドライン (2015)
  • Author(s): 竹下盛重(分担出筆）
  • Total Pages: 264
  • Publisher: 金原出版
• [Book] リンパ腫学 (2015)
  • Author(s): 竹下盛重(分担出筆）
  • Total Pages: 695
  • Publisher: 日本臨牀社